Chronic treatment of rats with lithium for two and three weeks decreased (3H)spiroperidol binding in the caudate nucleus by 26.3 and 26.9% respectively. One day after the termination of lithium treatment the binding was still 23.1% normal. Three days following termination of treatment it had recovered to normal levels. The in vitro addition of lithium to tissue homogenates from the striatum, cortex or hippocampus was found to inhibit the binding of (3H)QNB. This effect was reversible since washing the tissue to remove the lithium removed the inhibition. Chronic exposure of rats to lithium did not produce any permanent alterations in the density of the binding sites or the affinity of the muscarinic cholinergic receptors.